Comparative efficacy and safety of three fixed-ratio combination products in type 2 diabetes: A network meta-analysis

To systematically evaluate and compare the efficacy and safety of three fixed-ratio combination products-insulin degludec/liraglutide (IDegLira), insulin glargine/lixisenatide (iGlarLixi), and insulin degludec/insulin aspart (IDegAsp)-in patients with type 2 diabetes.

We systematically searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, and VIP up to July 2025 for randomized controlled trials (RCTs) comparing the three combinations of primary interest (IDegLira, iGlarLixi, IDegAsp) and their individual components (insulin degludec, insulin glargine, liraglutide, and lixisenatide). Inclusion of the individual components enabled indirect comparisons. Data extraction, risk-of-bias assessment, and GRADE evaluation were performed. Network meta-analysis was conducted using Stata 14.0, with treatments ranked by the surface under the cumulative ranking curve (SUCRA).

Twenty-one RCTs involving 12,815 patients were included. Both IDegLira (OR = 1.69, 95% CI: 1.08-2.65) and iGlarLixi (OR = 1.67, 95% CI: 1.17-2.37) had a higher incidence of treatment-emergent adverse events (TEAEs) than IDegAsp; no other significant pairwise differences were observed. Based on SUCRA values, which provide a probabilistic ranking (indicating the likelihood of being the best rather than direct statistical superiority), IDegLira had the highest probability of being optimal for reducing HbA1c (89.4%), fasting plasma glucose (81.8%), and incidence of hypoglycemic events (57.6%), while IDegAsp ranked highest regarding the incidence of TEAEs (97.9%). Inconsistency in the hypoglycemia network, likely due to varied definitions, warrants cautious interpretation.

Among the three fixed-ratio combination products, IDegLira appears most effective for glycemic control (in terms of HbA1c and FPG reduction), whereas IDegAsp demonstrates the best safety profile regarding incidence of TEAEs.